Tanshinone IIA potentiates the efficacy of 5-FU in Colo205 colon cancer cells in vivo through downregulation of P-gp and LC3-II

Abstract

Abstract. Traditional Chinese herbal medicines are widely accepted as an option for the treatment of colorectal cancers. Danshen (Salviae miltiorrhizae Radix) is widely prescribed in traditional Chinese medicine for cardiovascular diseases. Tanshinone IIA (Tan-IIA) is extracted from Danshen. Our previous studies have shown that Tan-IIA induces apoptosis in Colo205 human colon cancer cells in vitro and in vivo. In the present study, we investigated the efficacy of Tan-IIA and 5-fluorouracil (5-FU) in a Colo205 cell xenograft model. For in vivo studies, SCID mice were engrafted with Colo205 cells and from day 10 onwards were randomly divided into 3 groups and treated with 5-FU plus Tan-IIA, 5-FU plus corn oil, and the vehicle alone. At the end of a 4-week dosing schedule, the SCID mice were sacrificed and xenograft tumors were dissected for protein western blot analysis. Our results showed that the Colo205 xenograft model co-treated with Tan-IIA plus 5-FU caused a reduction in the xenograft tumor volumes and decreased P-glycoprotein (P-gp) and microtubule-associated protein light chain 3 (LC3)-II expression compared to 5-FU alone. Based on these observations, it may be possible to develop Tan-IIA plus 5-FU as therapeutic agents for human colon cancer.

Luteolin Induced-growth Inhibition and Apoptosis of Human Esophageal Squamous Carcinoma Cell Line Eca109 Cells in vitro

“…It's necessary to discover efficient pathway to impede the ectopic proliferation and accelerate death of tumor cells. Although, broad-spectrum anticancer drug such as 5-FU (a pyrimidine analogue) is widely used for clinical therapy (Gehoff et al, 2012;Pera et al, 2012;Su, 2012), the large side effects which it has been shown are a still limit aspect for use. Luteolin, a natural dietary flavonoid isolated from various plants has the potential role to slow or prevent the growth of tumor cell lines (Ko et al, 2002;Ju et al, 2007;Lim, et al, 2007;Chiu et al, 2008).…”

The Herbal Compound Cryptotanshinone Restores Sensitivity in Cancer Cells That Are Resistant to the Tumor Necrosis Factor-related Apoptosis-inducing Ligand

“…Among the major tanshinones isolated, cryptotanshinone, tanshinone I, tanshinone IIA, and dihydrotanshinone, tanshinone IIA have been shown to exert multiple anti-cancer activities including induction of * This work was supported by Hong Kong Baptist University Grants HKBU apoptosis and inhibition of angiogenesis and metastasis (8). Furthermore, tanshinones hold promise as sensitizing agents for chemotherapy and radiotherapy to enhance the cytotoxic effects of anti-cancer agents such as TNF-␣ (9), 5-fluorouracil (10), and ␥-irradiation (11). Recently, tanshinones have been found to induce ROS production in various types of cancer cells (12)(13)(14).…”

Tanshinone IIA enhances chemosensitivity of colon cancer cells by suppressing nuclear factor-κB

“…In addition, Fu et al (25) found that TSA blocked the epithelial-mesenchymal transition through the downregulation of hypoxia-inducible factor-1α, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines. In addition, increasing evidence indicated that TSA can inhibit tumor cell growth and induce apoptosis (15,17,43); however, despite the fact that in certain type of cancer evidence showed that intrinsic apoptosis pathways were involved (14,44) (46) found that TSA potentiated the efficacy of 5-FU in colon cancer cells in vivo through the downregulation of P-glycoprotein and LC3-II. The results of the present study confirmed the antitumor activity and chemosensitizing effect of TSA in colon cancer cells and provided new evidence that TSA can sensitize colon cancer cells to 5-FU through the suppression of NF-κB activation.…”